11.1 Introduction to CellsEssential idea: The evolution of multicellular organisms allowed cell specialization and cell replacement.The background image shows totipotent stem cells. These unspecialised cell will be divide and some will become the cells that form heart muscle, neurones in the brain and lymphocytes in the blood. These three types of specialised human cells are structurally very different and perform certain functions much more efficiently than an unspecialised cell, such as the embryonic cells above, could.Another advantage that multicellular organisms have over unicellular organisms is that severe damage to a cell does not mean the end of an organism. Stem cell persist through the life of a multi-cellular organism, this enables organisms to digest severely damaged cells and replace them, i.e. wounds can be healed.

2Understandings Statement Guidance 1.1.U1According to the cell theory, living organisms are composed of cells.1.1.U2Organisms consisting of only one cell carry out all functions of life in that cell.Students are expected to be able to name and briefly explain these functions of life: nutrition, metabolism, growth, response, excretion, homeostasis and reproduction.1.1.U3Surface area to volume ratio is important in the limitation of cell size.1.1.U4Multicellular organisms have properties that emerge from the interaction of their cellular components.1.1.U5Specialized tissues can develop by cell differentiation in multicellular organisms.1.1.U6Differentiation involves the expression of some genes and not others in a cell’s genome.1.1.U7The capacity of stem cells to divide and differentiate along different pathways is necessary in embryonic development and also makes stem cells suitable for therapeutic uses.

3Applications and SkillsStatementGuidance1.1.A1Questioning the cell theory using atypical examples, including striated muscle, giant algae and aseptate fungal hyphae.1.1.A2Investigation of functions of life in Paramecium and one named photosynthetic unicellular organism.Chlorella or Scenedesmus are suitable photosynthetic unicells, but Euglena should be avoided as it can feed heterotrophically.1.1.A3Use of stem cells to treat Stargardt’s disease and one other named condition.1.1.A4Ethics of the therapeutic use of stem cells from specially created embryos, from the umbilical cord blood of a new-born baby and from an adult’s own tissues.1.1.S1Use of a light microscope to investigate the structure of cells and tissues, with drawing of cells. Calculation of the magnification of drawings and the actual size of structures and ultrastructures shown in drawings or micrographs. (Practical 1)Scale bars are useful as a way of indicating actual sizes in drawings and micrographs.

41.1.S1 Use of a light microscope to investigate the structure of cells and tissues, with drawing of cells. Calculation of the magnification of drawings and the actual size of structures and ultrastructures shown in drawings or micrographs. (Practical 1)Microscopes are best learn through experience the below links are primarily for those without access to a microscope.Learn about Microscopes:Virtual microscope:Source: https://microbewiki.kenyon.edu/index.php/Dinoflagellata

111.1.U1 According to the cell theory, living organisms are composed of cells.Cell theory states that:All living things are composed of cells (or cell products)The cell is the smallest unit of lifeCells only arise from pre-existing cellsSource:

121.1.U1 According to the cell theory, living organisms are composed of cells.All living things are composed of cells (or cell products)Longitudinal section of a root tip of Maize (Zea mays)by Science and Plants for Schools on Flickr (CC)

131.1.U1 According to the cell theory, living organisms are composed of cells.The cell is the smallest unit of lifeSpecialized structures within cells (organelles) carry out different functions. Organelles cannot survive alone.This micrograph of a Paramecium shows the 2 contractile vacuoles, the oral groove with the formation of a new food vacuole at its end, and the overall surrounding cilia.Source:

141.1.U1 According to the cell theory, living organisms are composed of cells.Cells only arise from pre-existing cells:Cells multiply through divisionAll life evolved from simpler ancestorsMitosis results in genetically identical diploid daughter cellsMeiosis generates haploid gametes (sex cells)4-cell stage of a sea biscuit by Bruno Vellutini on Flickr (CC)

151.1.A1 Questioning the cell theory using atypical examples, including striated muscle, giant algae and aseptate fungal hyphae.striated musclechallenges the idea that a cell has one nucleusMuscle cells have more than one nucleus per cellMuscle Cells called fibres can be very long (300mm)They are surrounded by a single plasma membrane but they are multi-nucleated (many nuclei).This does not conform to the standard view of a small single nuclei within a cellSource:

161.1.A1 Questioning the cell theory using atypical examples, including striated muscle, giant algae and aseptate fungal hyphae.aseptate fungal hyphaechallenges the idea that a cell is a single unit.Fungal hyphae are again very large with many nuclei and a continuous cytoplasmThe tubular system of hyphae form dense networks called myceliumLike muscle cells they are multi-nucleatedThey have cell walls composed of chitinThe cytoplasm is continuous along the hyphae with no end cell wall or membraneSource:

171.1.A1 Questioning the cell theory using atypical examples, including striated muscle, giant algae and aseptate fungal hyphae.giant algae (Acetabularia)Acetabularia is a single-celled organism that challenges both the idea that cells must be simple in structure and small in sizeGigantic in size (5 – 100mm)Complex in form, it consists of three anatomical parts:Bottom rhizoid (that resembles a set of short roots)Long stalkTop umbrella of branches that may fuse into a capThe single nucleus is located in the rhizoidSource:

181.1.U2 Organisms consisting of only one cell carry out all functions of life in that cell.You probably know:In this course the functions are refined:MovementReproductionSensitivityHomeostasisGrowthRespirationExcretionNutritionMetabolism - the web of all the enzyme-catalysed reactions in a cell or organism, e.g. respirationResponse - Living things can respond to and interact with the environmentHomeostasis - The maintenance and regulation of internal cell conditions, e.g. water and pHGrowth - Living things can grow or change size / shapeExcretion – the removal of metabolic wasteReproduction - Living things produce offspring, either sexually or asexuallyNutrition – feeding by either the synthesis of organic molecules (e.g. photosynthesis) or the absorption of organic matter

191.1.U2 Organisms consisting of only one cell carry out all functions of life in that cell.Remembering the functions of lifeAn easy way to remember Metabolism, Response, Homeostasis, Growth, Reproduction, Excretion and Nutrition is:“MR H GREN”(each letter is a function of life)Source:

201.1.A2 Investigation of functions of life in Paramecium and one named photosynthetic unicellular organism.How does this paramecium show the functions of life?Source:

211.1.A2 Investigation of functions of life in Paramecium and one named photosynthetic unicellular organism.Excretion – the plasma membrane control the entry and exit of substances including expulsion of metabolic wasteHomeostasis – contractile vacuole fill up with water and expel I through the plasma membrane to manage the water contentResponse – the wave action of the cilia moves the paramecium in response to changes in the environment, e.g. towards food.Source:Metabolism – most metabolic pathways happen in the cytoplasmNutrition – food vacuoles contain organisms the parameium has consumedGrowth – after consuming and assimilating biomass from food the paramecium will get larger until it divides.Reproduction – The nucleus can divide to support cell division by mitosis, reproduction is often asexual

221.1.A2 Investigation of functions of life in Paramecium and one named photosynthetic unicellular organism.How does this algae show the functions of life?Source:

231.1.A2 Investigation of functions of life in Paramecium and one named photosynthetic unicellular organism.Excretion – the plasma membrane control the entry and exit of substances including the difussion out of waste oxygenReproduction – The nucleus can divide to support cell division, by mitosis (these cells are undergoing cytokinesis)Response – the wave action of the cilia moves the algae in response to changes in the environment, e.g. towards light.Source:Metabolism – most metabolic pathways happen in the cytoplasmHomeostasis – contractile vacuole fill up with water and expel I through the plasma membrane to manage the water contentNutrition – photosynthesis happens inside the chloroplasts to provide the algae with foodGrowth – after consuming and assimilating biomass from food the algae will get larger until it divides.

241.1.U3 Surface area to volume ratio is important in the limitation of cell size.

251.1.U3 Surface area to volume ratio is important in the limitation of cell size.

261.1.U3 Surface area to volume ratio is important in the limitation of cell size.

271.1.U3 Surface area to volume ratio is important in the limitation of cell size.Cells and tissues specialised for gas or material exchange will increase their surface area to optimise the transfer of materials, e.g. microvilli (below) in the small intestineThe cell must consequently divide in order to restore a viable SA:Vol ratio and survive.A represents a small single celled organismB a large single celled organismC multicellular organismABC

281.1.U3 Surface area to volume ratio is important in the limitation of cell size.In summary:The rate of metabolism of a cell is a function of its mass / volumeThe rate of material exchange in and out of a cell is a function of its surface areaAs the cell grows, volume increases faster than surface area (leading to a decreased SA:Vol ratio)If the metabolic rate is greater than the rate of exchange of vital materials and wastes, the cell will eventually dieHence the cell must consequently divide in order to restore a viable SA:Vol ratio and surviveCells and tissues specialised for gas or material exchange (e.g. alveoli) will increase their surface area to optimise the transfer of materialsExtension: Can you think of any exceptions? See if you can find out about unusually large cells and how they are adapted to survive.

291.1.U4 Multicellular organisms have properties that emerge from the interaction of their cellular components.Emergent properties arise from the interaction of component parts. The whole is greater than the sum of its parts. Multicellular organisms are capable of completing functions that individual cells could not undertake - this is due to the interaction between cells producing new functions.

301.1.U4 Multicellular organisms have properties that emerge from the interaction of their cellular components.Science traditionally has been taken a reductionist approach to solving problems and developing theories. Systems Biology uses inductive thinking as it is realised the importance of emergent properties, whether it be the interaction of genes, enzymes working together in a metabolic pathway, or cells forming tissues, different tissues forming organs, in turn forming organ systems and then the organism itself. At each level emergent properties arise.

311.1.U4 Multicellular organisms have properties that emerge from the interaction of their cellular components.As a model consider the electric light bulb. The bulb is the system and is composed of a filament made of tungsten, a metal cup, and a glass container. We can study the parts individually how they function and the properties they posses. These would be the properties of :TungstenMetal cupGlass containerWhen studied individually they do not allow the prediction of the properties of the light bulb. Only when we combine them to form the bulb can these properties be determined. There is nothing supernatural about the emergent properties rather it is simply the combination of the parts that results in new properties emerging.Source:

321.1.U6 Differentiation involves the expression of some genes and not others in a cell’s genome.All (diploid) cells of an individual organisms share an identical genome - each cell contains the entire set of genetic instructions for that organismBUT not all genes are expressed (activated) in all cellsIn (totipotent) embryonic stem cells the entire genome is activeNewly formed cells receive signals which deactivate (or more rarely activate) genes, e.g. a skin cell does not need to be able to produce haemoglobin (the pigment in red blood cells that carries oxygen)Screenshot from this excellent tutorial:

331.1.U6 Differentiation involves the expression of some genes and not others in a cell’s genome.Extension: Active genes are usually packaged in an expanded and accessible form (euchromatin), while inactive genes are mainly packaged in a condensed form (heterochromatin)The fewer active genes a cell possesses the more specialised it will becomeAs a result of gene expression cell differentiation begins: the cell’s metabolism and shape changes to carry out a specialised function.Screenshot from this excellent tutorial:

341.1.U5 Specialized tissues can develop by cell differentiation in multicellular organisms.In humans 220 distinct highly specialised cell types have been recognisedAll specialised cells and the organs constructed from them have developed as a result of differentiationSource:

351.1.U7 The capacity of stem cells to divide and differentiate along different pathways is necessary in embryonic development and also makes stem cells suitable for therapeutic uses.Stem cells are unspecialised cells that can:Can continuously divide and replicateHave the capacity to differentiate into specialised cell typesTotipotentCan differentiate into any type of cell.PluripotentCan differentiate into manytypes of cell.MultipotentCan differentiate into a few closely-related types of cell.UnipotentCan regenerate but can only differentiate into their associated cell type(e.g. liver stem cells can only make liver cells).Image from:

36Learn about stem cells using the tutorials1.1.U7 The capacity of stem cells to divide and differentiate along different pathways is necessary in embryonic development and also makes stem cells suitable for therapeutic uses.Learn about stem cells using the tutorialsA Stem Cell Story

37Stargardt's macular dystrophy1.1.U7 Use of stem cells to treat Stargardt’s disease and one other named condition.Stargardt's macular dystrophyThe problemAffects around one in 10,000 childrenRecessive genetic (inherited) conditionThe mutation causes an active transport protein on photoreceptor cells to malfunctionThe photoreceptor cells degeneratethe production of a dysfunctional protein that cannot perform energy transportthat causes progressive, and eventually total, loss of central visionThe treatmentEmbryonic stem cells are treated to divide and differntiate to become retinal cellsThe retinal cells are injected into the retinaThe retinal cells attach to the retina and become functionalCentral vision improves as a result of more functional retinal cellsThe futureThis treatment is still in at the stage of limited clinical trials, but will likely be in usage in the future

38Learn about stem cell therapies using the tutorials1.1.U7 Use of stem cells to treat Stargardt’s disease and one other named condition.Learn about stem cell therapies using the tutorials

391.1.U7 Use of stem cells to treat Stargardt’s disease and one other named condition.LeukemiaThe problemCancer of the blood or bone marrow, resulting in abnormally high levels of poorly-functioning white blood cells.The treatmentHematopoetic Stem Cells (HSCs) are harvested from bone marrow, peripheral blood or umbilical cord bloodChemotherapy and radiotherapy used to destroy the diseased white blood cellsNew white blood cells need to be replaced with healthy cells.HSCs are transplanted back into the bone marrowHSCs differentiate to form new healthy white blood cellsThe benefitThe use of a patient’s own HSCs means there is far less risk of immune rejection than with a traditional bone marrow transplant.

40Comparison of stem cell sources1.1.A4 Ethics of the therapeutic use of stem cells from specially created embryos, from the umbilical cord blood of a new-born baby and from an adult’s own tissues.Comparison of stem cell sourcesEmbryoCord bloodAdultEase of extractionCan be obtained from excess embryos generated by IVF programs.Easily obtained and stored. Though limited quantities availableDifficult to obtain as there are very few and are buried deep in tissuesEthics of the extractionCan only be obtained by destruction of an embryoUmbilical cord is removed at birth and discarded whether or not stem cells are harvestedAdult patient can give permission for cells to be extractedGrowth potentialAlmost unlimitedReduced potential (compared to embryonic cells)Tumor riskHigher risk of developmentLower risk of development

41Comparison of stem cell sources1.1.A4 Ethics of the therapeutic use of stem cells from specially created embryos, from the umbilical cord blood of a new-born baby and from an adult’s own tissues.Comparison of stem cell sourcesEmbryoCord bloodAdultDifferentiationCan differentiate into any cell typeLimited capacity to differentiate (without inducement only naturally divide into blood cells)Limited capacity to differentiate (dependent on the source tissue)Genetic damageLess chance of genetic damage than adult cellsDue to accumulation of mutations through the life of the adult genetic damage can occurCompatibilityStem cells are not genetically identical to the patientFully compatible with the patient as the stem cells are genetically identical

42Arguments for Therapeutic Cloning1.1.A4 Ethics of the therapeutic use of stem cells from specially created embryos, from the umbilical cord blood of a new-born baby and from an adult’s own tissues.Arguments for Therapeutic CloningStem cell research may pave the way for future discoveries and beneficial technologies that would not have occurred if their use had been bannedMay be used to cure serious diseases or disabilities with cell therapy (replacing bad cells with good ones)Transplants are less likely to be rejected as they are cells which are genetically identical to the parentTransplants do not require the death of another humanStem cells can be taken from embryos that have stopped developing and would have died anyway (e.g. abortions)Cells are taken at a stage when the embryo has no nervous system and can arguably feel no painStem cells can be created without the need for fertilisation and destruction of ‘natural’ human embryos – induced pluripotent stem cells

43Arguments Against Therapeutic Cloning1.1.A4 Ethics of the therapeutic use of stem cells from specially created embryos, from the umbilical cord blood of a new-born baby and from an adult’s own tissues.Arguments Against Therapeutic CloningInvolves the creation and destruction of human embryos (at what point do we afford the right to life?)Embryonic stem cells are capable of continued division and may develop into cancerous cells and cause tumorsMore embryos are generally produced than are needed, so excess embryos are killedWith additional cost and effort, alternative technologies may fulfill similar roles (e.g. nuclear reprogramming of differentiated cell lines)Religious or moral objections due to the ‘playing God’ argument.The embryo which is created could potentially be used in IVF and develop into a human fetus, so are we creating human life to destroy it?Although cloning humans reproductively is illegal, this has not been ratified by all nations. Potential for a race to clone the first human.

441.1.A4 Ethics of the therapeutic use of stem cells from specially created embryos, from the umbilical cord blood of a new-born baby and from an adult’s own tissues.

45Check out the news – there are new stories on iPS all the time1.1.A4 Ethics of the therapeutic use of stem cells from specially created embryos, from the umbilical cord blood of a new-born baby and from an adult’s own tissues.Check out the news – there are new stories on iPS all the time